Summary The effect of LiCI on melanoma cell growth and differentiationl was studied in mouse and human melanoma cell lines. LiCI markedly inhibited B16 and HT-144 melanoma cell growth in iitro. Clonogenicity in soft agar of the melanoma cells was also markedly inhibited by LiCl. Pretreatmelnt of B16 mouse melanoma cells with LiCl delayed the appearance of melanoma tumours in syngeneic mice. Growth (Ptashne et al., 1980;Hori & Oka, 1979;Rybak & Stockdale, 1981). This agent also potentiated the mitogenic response of B and T cells (Hart 1981(Hart , 1982 Bray et al., '981).LiCl was found to modulate haematopoiesis by influencing pluripotential and committed stem cell proliferation and differentiation toward granulocytes (Gallicchio & Chen, 1981; Morley & Galbraith, 1978;Levitt & Quesenberg, 1980). Axolotl-embryo's ectodermal cells were induced to differentiate into mesenchyme, nerve cells and melanophores by LiCl (Lovtrop & Perris, 1983). LiCI has also been shown to potentiate the anti-melanoma effect of bleomycin in mice bearing melanoma tumours (Ballin et al., 1983).The biochemical basis of lithium's actions on cell growth and differentiation is unknown. However, in different tissues lithium has been shown to affect cyclic nucleotide levels (Dovsa & Mecher, 1970;Wang et al., 1974) glucose metabolism (Nordenberg et al., 1982; Dempsey et al., 1976) and phosphatidylinositol metabolism (Allison & Stewart, 1971; Allison et al., 1976; Berridge & Irvine, 1984 Cell growitth e:xperinments In most cases 105 cells were plated in 1.5ml culture medium, in 3.5cm culture dishes. When cells were cultured for more than 3 days, 3 x 104 cells were plated in 10ml culture medium in 8.5cm culture dishes. This was done to avoid cell crowding. Two to four hours later, after most cells were attached to the bottom of the petri dish, LiCI or myoinositol were added as indicated in legend to Figure 1 and